Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes
Growing evidence indicates important roles for astrocytes in neurodevelopment and diseases. However, astrocytes and their roles in these processes remain poorly understood. Despite recent progress in reprogramming somatic cells into different types of neural cells, reprogramming to astrocytes has la...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-07-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716307963 |
| _version_ | 1818512743816232960 |
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| author | E Tian Guoqiang Sun Guihua Sun Jianfei Chao Peng Ye Charles Warden Arthur D. Riggs Yanhong Shi |
| author_facet | E Tian Guoqiang Sun Guihua Sun Jianfei Chao Peng Ye Charles Warden Arthur D. Riggs Yanhong Shi |
| author_sort | E Tian |
| collection | DOAJ |
| description | Growing evidence indicates important roles for astrocytes in neurodevelopment and diseases. However, astrocytes and their roles in these processes remain poorly understood. Despite recent progress in reprogramming somatic cells into different types of neural cells, reprogramming to astrocytes has lagged. Here, we show that functional astrocytes can be generated from mammalian fibroblasts using only small molecules. Induced mouse astrocytes resemble primary astrocytes in astrocytic gene expression and epigenomic status and exhibit functional properties in promoting neuronal maturation, glutamate uptake, and calcium signaling. Moreover, these cells can recapitulate the Alexander disease phenotype of protein aggregation when expressing Gfap with a disease-causing mutation. The same compounds can also reprogram human fibroblasts into astroglial progenitor cells that can further mature into functional astrocytes. These chemically induced astrocytes may provide cellular models to uncover roles of astrocytes in normal neurodevelopment and pathogenesis of neurological diseases. |
| first_indexed | 2024-12-10T23:51:21Z |
| format | Article |
| id | doaj.art-80d2945396f4480fb41d01a2b3d8f7ec |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T23:51:21Z |
| publishDate | 2016-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-80d2945396f4480fb41d01a2b3d8f7ec2022-12-22T01:28:45ZengElsevierCell Reports2211-12472016-07-0116378179210.1016/j.celrep.2016.06.042Small-Molecule-Based Lineage Reprogramming Creates Functional AstrocytesE Tian0Guoqiang Sun1Guihua Sun2Jianfei Chao3Peng Ye4Charles Warden5Arthur D. Riggs6Yanhong Shi7Division of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USADivision of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USADiabetes and Metabolism Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USADivision of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USADivision of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USAIntegrative Genomics Core, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USADiabetes and Metabolism Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USADivision of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USAGrowing evidence indicates important roles for astrocytes in neurodevelopment and diseases. However, astrocytes and their roles in these processes remain poorly understood. Despite recent progress in reprogramming somatic cells into different types of neural cells, reprogramming to astrocytes has lagged. Here, we show that functional astrocytes can be generated from mammalian fibroblasts using only small molecules. Induced mouse astrocytes resemble primary astrocytes in astrocytic gene expression and epigenomic status and exhibit functional properties in promoting neuronal maturation, glutamate uptake, and calcium signaling. Moreover, these cells can recapitulate the Alexander disease phenotype of protein aggregation when expressing Gfap with a disease-causing mutation. The same compounds can also reprogram human fibroblasts into astroglial progenitor cells that can further mature into functional astrocytes. These chemically induced astrocytes may provide cellular models to uncover roles of astrocytes in normal neurodevelopment and pathogenesis of neurological diseases.http://www.sciencedirect.com/science/article/pii/S2211124716307963direct conversionchemical reprogramminginduced astrocytessmall moleculesAlexander disease |
| spellingShingle | E Tian Guoqiang Sun Guihua Sun Jianfei Chao Peng Ye Charles Warden Arthur D. Riggs Yanhong Shi Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes Cell Reports direct conversion chemical reprogramming induced astrocytes small molecules Alexander disease |
| title | Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes |
| title_full | Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes |
| title_fullStr | Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes |
| title_full_unstemmed | Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes |
| title_short | Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes |
| title_sort | small molecule based lineage reprogramming creates functional astrocytes |
| topic | direct conversion chemical reprogramming induced astrocytes small molecules Alexander disease |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716307963 |
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